9 th Annual Conference of the International FES Society September 2004 – Bournemouth, UK Efficacy of Intraspinal Microstimulation in Restoring Stepping after Spinal Cord Injury Mushahwar VK 1,2 , Saigal R 3 , Bamford J 2 , Guevremont LG 1,2 , Norton JA 1,2 1 Department of Biomed Engr and 2 Cntr for Neurosci, Univ Alberta, Edmonton, AB, Canada 3 Division of Health Sciences and Technology, Harvard-MIT, Cambridge, MA, USA Email: Vivian.mushahwar@ualberta.ca Website: www.ualberta.ca/~vmushahw/ Abstract The goal of this project was to test the efficacy of intraspinal microstimulation (ISMS) in restoring leg movements after spinal cord injury (SCI). Three aspects of ISMS-generated movements were tested: 1) kinematics and kinetics of evoked stepping, 2) fatigue resistance and muscle fiber-type recruitment, and 3) long-term stability of stimulation parameters and elicited responses. Studies were conducted in cats with long-term SCI and intact rats. ISMS evoked near-normal stepping that was fully weight-bearing and fatigue resistant in paralyzed cats. More than 60% of muscle fibers activated with ISMS in rats were slow and fast, fatigue-resistant. In contrast, 85% of fibers activated with epineural stimulation through cuff electrodes were fast, fatiguable. In one cat with SCI, ISMS microwires were implanted for 6 months. Stimulus threshold remained constant throughout the period of implantation. Hind limb responses were dominated by flexor contractions over the first 8 weeks post-injury, during which spinal shock and hyperreflexia were manifest. In the proceeding 4 months, ISMS evoked a full repertoire of stable and predictable limb movements. The findings suggest that ISMS may be a viable electrical stimulation approach for restoring leg movements after SCI. 1 Introduction Intraspinal microstimulation was suggested as a potential functional electrical stimulation (FES) technique for restoring standing and walking after SCI [1]. The lumbar enlargement, which is 5 cm-long in humans, is the target region for implantation. This region contains motoneurons innervating all lower extremity muscles as well as a large proportion of the neuronal networks involved in locomotion. By tapping into this “control center” in the cord, one can take advantage of built-in networks which generate synergistic leg movements. We previously demonstrated that ISMS microwires chronically implanted in intact cats remain securely in place throughout the period of implantation [2]. Stimulation thresholds, ranging between 2-30 μA in amplitude, doubled over the first 4 weeks post implantation, presumably due to natural encapsulation processes, and remained constant thereafter. Stimulation through at least 67% of the microwires in each animal continued to elicit consistent limb movements [2]. These findings highlighted the feasibility of ISMS as a potential FES approach. The present preliminary studies investigated the efficacy of ISMS in restoring stepping after complete SCI. Three separate studies were conducted concurrently to test 1) the capacity of ISMS to restore functional stepping after chronic SCI, 2) the fatigue resistance of evoked stepping and muscle fiber-type recruitment, and 3) the long- term stability of ISMS parameters and elicited responses after SCI. 2 Methods Experimental protocols were approved by Univ. Alberta Animal Welfare Committee. 2.1 ISMS-evoked stepping after SCI Adult cats (n=4) were spinalized at T11, using aseptic surgical techniques. Buprenorphine was administered 3x per day for 2-3 days to ensure comfortable recovery. Bladders were manually expressed twice daily and muscles of the hind limbs were stretched. Two to four weeks later, acute experiments were conducted during which microwires were implanted bilaterally in the lumbar enlargement under isoflurane anesthesia. Microwire implantation followed published techniques [2, 3] and targeted regions of the ventral horn that generate hip, knee, and ankle flexor or extensor movements when electrically stimulated [4]. The cats were then